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Brain Sciences May 2024Patients with borderline personality disorder (BPD) report to be especially prone to social emotions like shame and guilt. At the same time, these emotions seem to play...
OBJECTIVE
Patients with borderline personality disorder (BPD) report to be especially prone to social emotions like shame and guilt. At the same time, these emotions seem to play an important role in BPD pathology. The present study aimed to deepen the knowledge about the processes behind shame and guilt in patients with BPD.
METHODS
Twenty patients with BPD and twenty healthy controls (HCs) took part in an experiment that induced shame and guilt by imagining scenarios during scanning using functional brain imaging. Participants also filled out self-report questionnaires and took part in diagnostic interviews.
RESULTS
BPD patients reported more proneness to guilt but not to shame than the HCs. There was no difference in the self-reported intensity rating of experimentally induced emotions between the groups. Between-group contrast of neural signals in the shame condition revealed a stronger activation of cingulate and fusiform gyrus for the BPD patients compared to the controls, and a more pronounced activation in the lingual gyrus and cuneus for the HCs. In the guilt condition, activation in the caudate nucleus, the fusiform gyrus, and the posterior cingulate cortex was stronger in BPD patients, while HC showed stronger activations in cuneus, lingual gyrus, and fronto-temporal regions.
CONCLUSIONS
Differences in the neuro-functional processes between BPD patients and HC were found, even though the two groups did not differ in their self-report of subjective proneness to guilt and emotional intensity of shame and guilt during the experiment. While the HCs may be engaged more by the emotional scenarios themselves, the BPD patients may be more occupied with cognitive regulatory and self-referential processing.
PubMed: 38928549
DOI: 10.3390/brainsci14060549 -
Cancers Jun 2024Cancer is characterized by increased metabolic activity and vascularity, leading to temperature changes in cancerous tissues compared to normal cells. This study focused...
Cancer is characterized by increased metabolic activity and vascularity, leading to temperature changes in cancerous tissues compared to normal cells. This study focused on patients with abnormal mammogram findings or a clinical suspicion of breast cancer, exclusively those confirmed by biopsy. Utilizing an ultra-high sensitivity thermal camera and prone patient positioning, we measured surface temperatures integrated with an inverse modeling technique based on heat transfer principles to predict malignant breast lesions. Involving 25 breast tumors, our technique accurately predicted all tumors, with maximum errors below 5 mm in size and less than 1 cm in tumor location. Predictive efficacy was unaffected by tumor size, location, or breast density, with no aberrant predictions in the contralateral normal breast. Infrared temperature profiles and inverse modeling using both techniques successfully predicted breast cancer, highlighting its potential in breast cancer screening.
PubMed: 38927969
DOI: 10.3390/cancers16122264 -
Bioengineering (Basel, Switzerland) May 2024Bone marrow edema-like lesions (BMEL) in the knee have been linked to the symptoms and progression of osteoarthritis (OA), a highly prevalent disease with profound...
Bone marrow edema-like lesions (BMEL) in the knee have been linked to the symptoms and progression of osteoarthritis (OA), a highly prevalent disease with profound public health implications. Manual and semi-automatic segmentations of BMELs in magnetic resonance images (MRI) have been used to quantify the significance of BMELs. However, their utilization is hampered by the labor-intensive and time-consuming nature of the process as well as by annotator bias, especially since BMELs exhibit various sizes and irregular shapes with diffuse signal that lead to poor intra- and inter-rater reliability. In this study, we propose a novel unsupervised method for fully automated segmentation of BMELs that leverages conditional diffusion models, multiple MRI sequences that have different contrast of BMELs, and anomaly detection that do not rely on costly and error-prone annotations. We also analyze BMEL segmentation annotations from multiple experts, reporting intra-/inter-rater variability and setting better benchmarks for BMEL segmentation performance.
PubMed: 38927762
DOI: 10.3390/bioengineering11060526 -
Genes Jun 2024Deficiencies in DNA mismatch repair (MMRd) leave characteristic footprints of microsatellite instability (MSI) in cancer genomes. We used data from the Cancer Genome...
Deficiencies in DNA mismatch repair (MMRd) leave characteristic footprints of microsatellite instability (MSI) in cancer genomes. We used data from the Cancer Genome Atlas and International Cancer Genome Consortium to conduct a comprehensive analysis of MSI-associated cancers, focusing on indel mutational signatures. We classified MSI-high genomes into two subtypes based on their indel profiles: deletion-dominant (MMRd-del) and insertion-dominant (MMRd-ins). Compared with MMRd-del genomes, MMRd-ins genomes exhibit distinct mutational and transcriptomic features, including a higher prevalence of T>C substitutions and related mutation signatures. Short insertions and deletions in MMRd-ins and MMRd-del genomes target different sets of genes, resulting in distinct indel profiles between the two subtypes. In addition, indels in the MMRd-ins genomes are enriched with subclonal alterations that provide clues about a distinct evolutionary relationship between the MMRd-ins and MMRd-del genomes. Notably, the transcriptome analysis indicated that MMRd-ins cancers upregulate immune-related genes, show a high level of immune cell infiltration, and display an elevated neoantigen burden. The genomic and transcriptomic distinctions between the two types of MMRd genomes highlight the heterogeneity of genetic mechanisms and resulting genomic footprints and transcriptomic changes in cancers, which has potential clinical implications.
Topics: Humans; Microsatellite Instability; INDEL Mutation; Neoplasms; DNA Mismatch Repair; Genome, Human; Transcriptome
PubMed: 38927706
DOI: 10.3390/genes15060770 -
Genes May 2024Azoospermia is a form of male infertility characterized by a complete lack of spermatozoa in the ejaculate. Sertoli cell-only syndrome (SCOS) is the most severe form of...
Azoospermia is a form of male infertility characterized by a complete lack of spermatozoa in the ejaculate. Sertoli cell-only syndrome (SCOS) is the most severe form of azoospermia, where no germ cells are found in the tubules. Recently, FANCM gene variants were reported as novel genetic causes of spermatogenic failure. At the same time, FANCM variants are known to be associated with cancer predisposition. We performed whole-exome sequencing on a male patient diagnosed with SCOS and a healthy father. Two compound heterozygous missense mutations in the FANCM gene were found in the patient, both being inherited from his parents. After the infertility assessment, the patient was diagnosed with diffuse astrocytoma. Immunohistochemical analyses in the testicular and tumor tissues of the patient and adequate controls showed, for the first time, not only the existence of a cytoplasmic and not nuclear pattern of FANCM in astrocytoma but also in non-mitotic neurons. In the testicular tissue of the SCOS patient, cytoplasmic anti-FANCM staining intensity appeared lower than in the control. Our case report raises a novel possibility that the infertile carriers of FANCM gene missense variants could also be prone to cancer development.
Topics: Humans; Male; Astrocytoma; Sertoli Cell-Only Syndrome; Mutation, Missense; Adult; Exome Sequencing; DNA Helicases; Azoospermia
PubMed: 38927643
DOI: 10.3390/genes15060707 -
Biomedicines Jun 2024Arteriovenous malformations (AVMs) are vascular malformations that are prone to rupturing and can cause significant morbidity and mortality in relatively young patients.... (Review)
Review
Arteriovenous malformations (AVMs) are vascular malformations that are prone to rupturing and can cause significant morbidity and mortality in relatively young patients. Conventional treatment options such as surgery and endovascular therapy often are insufficient for cure. There is a growing body of knowledge on the genetic and molecular underpinnings of AVM development and maintenance, making the future of precision medicine a real possibility for AVM management. Here, we review the pathophysiology of AVM development across various cell types, with a focus on current and potential druggable targets and their therapeutic potentials in both sporadic and familial AVM populations.
PubMed: 38927496
DOI: 10.3390/biomedicines12061289 -
BMC Zoology Jun 2024Many animals appear to preferentially renest in proximity to a site they previously occupied. Evidence of nest fidelity is often inferred from a right skewed...
BACKGROUND
Many animals appear to preferentially renest in proximity to a site they previously occupied. Evidence of nest fidelity is often inferred from a right skewed distribution of distances between the nests of individuals that breed in two consecutive reproduction episodes, where many individuals nest some arbitrarily close distance to their prior nest and others, in the extended right tail of the distribution, nest far from the nest they previously occupied. Because right skewed distributions of inter-nest distances can arise even when individuals choose nest locations randomly, however, such inferences are prone to error. The importance of null models-used to generate patterns of individual inter-nest distances by processes that do not involve site attachment-for inferences about site fidelity has been known for decades but is still often unappreciated or ignored.
METHODS
The right skewed distributions of inter-nest distances observed in two earlier studies of male smallmouth bass (Micropterus dolomieu) suggest prima facie that males exhibit nest site fidelity between annual reproduction episodes, but patterns of inter-nest distances have yet to be compared to an adequate null model. Here, we evaluate the nest site fidelity of marked male M. dolomieu in a decade-long dataset, where we apply a randomization procedure based on the rencontre probability problem to generate null models. Eight observed distributions of individual, annual inter-nest distances are compared to a year-specific null model to determine whether random processes are sufficient to explain the observed distributions of inter-nest distances.
RESULTS
Through contrasts between observed annual inter-nest distances and results derived from null models that imposed realistic constraints on behavior, we show that some males were undoubtedly nest-site faithful. To reinforce the utility of null models and to make these kinds of models more accessible, we also provide a supplemental tutorial. The tutorial illustrates how random site choices, subject to common ecological and behavioral constraints, and even how distance is measured, can produce patterns of inter-nest distances that falsely imply nest site fidelity, or a lack of fidelity. The R code needed to reproduce these null models is included. The inference errors evident in our examples generalize to other forms of site fidelity, such as the apparent patch fidelity of certain sea bird foragers.
CONCLUSIONS
The comparisons of observed distributions of inter-nest distances with those generated by null models imply that, as suggested in prior studies, male M. dolomieu indeed exhibit annual nest site fidelity. Procedures like those we apply are necessary first steps in analyses when distributions of distances between the nests of individuals in consecutive reproduction episodes are used to infer nest-site fidelity. Why male M. dolomieu are site faithful is a question yet to be answered.
PubMed: 38926870
DOI: 10.1186/s40850-024-00205-z -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2024To assess the effectiveness and safety of prone positioning in the treatment of neonatal respiratory distress syndrome (NRDS) using invasive respiratory support. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To assess the effectiveness and safety of prone positioning in the treatment of neonatal respiratory distress syndrome (NRDS) using invasive respiratory support.
METHODS
A prospective study was conducted from June 2020 to September 2023 at Suining County People's Hospital, involving 77 preterm infants with gestational ages less than 35 weeks requiring invasive respiratory support for NRDS. The infants were randomly divided into a supine group (37 infants) and a prone group (40 infants). Infants in the prone group were ventilated in the prone position for 6 hours followed by 2 hours in the supine position, continuing in this cycle until weaning from the ventilator. The effectiveness and safety of the two approaches were compared.
RESULTS
At 6 hours after enrollment, the prone group showed lower arterial blood carbon dioxide levels, inspired oxygen concentration, oxygenation index, rates of tracheal intubation bacterial colonization, and Neonatal Pain, Agitation and Sedation Scale scores compared to the supine group (<0.05). There were no significant differences between the groups in terms of pH, arterial oxygen pressure, positive end-expiratory pressure, duration of mechanical ventilation, accidental extubation, ventilator-associated pneumonia, air leak syndrome, skin pressure sores, feeding intolerance, and grades II-IV intraventricular hemorrhage (>0.05).
CONCLUSIONS
Compared to supine positioning, prone ventilation effectively improves oxygenation, increases comfort, and reduces tracheal intubation bacterial colonization in neonates requiring mechanical ventilation for NRDS, without significantly increasing adverse reactions.
Topics: Humans; Prone Position; Infant, Newborn; Respiratory Distress Syndrome, Newborn; Male; Female; Prospective Studies; Respiration, Artificial
PubMed: 38926379
DOI: 10.7499/j.issn.1008-8830.2312126 -
Cell Death & Disease Jun 2024Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is prone to metastasis and therapy resistance. Owing to its aggressive nature and limited...
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is prone to metastasis and therapy resistance. Owing to its aggressive nature and limited availability of targeted therapies, TNBC is associated with higher mortality as compared to other forms of breast cancer. In order to develop new therapeutic options for TNBC, we characterized the factors involved in TNBC growth and progression. Here, we demonstrate that N-acylsphingosine amidohydrolase 1 (ASAH1) is overexpressed in TNBC cells and is regulated via p53 and PI3K-AKT signaling pathways. Genetic knockdown or pharmacological inhibition of ASAH1 suppresses TNBC growth and progression. Mechanistically, ASAH1 inhibition stimulates dual-specificity phosphatase 5 (DUSP5) expression, suppressing the mitogen-activated protein kinase (MAPK) pathway. Furthermore, pharmacological cotargeting of the ASAH1 and MAPK pathways inhibits TNBC growth. Collectively, we unmasked a novel role of ASAH1 in driving TNBC and identified dual targeting of the ASAH1 and MAPK pathways as a potential new therapeutic approach for TNBC treatment.
Topics: Humans; Triple Negative Breast Neoplasms; Acid Ceramidase; Dual-Specificity Phosphatases; Female; Cell Line, Tumor; MAP Kinase Signaling System; Cell Proliferation; Animals; Gene Expression Regulation, Neoplastic; Mice, Nude; Mice; Proto-Oncogene Proteins c-akt; Tumor Suppressor Protein p53; Phosphatidylinositol 3-Kinases; Signal Transduction
PubMed: 38926346
DOI: 10.1038/s41419-024-06831-2 -
PloS One 2024This study aims to establish the validity and reliability of the prone Yo-YoIRL1 in elite female rugby league players (part one) and determine the anthropometric and...
Validity, reliability, and the contributing physical characteristics of a modified 15m prone Yo-Yo Intermittent Recovery Test Level-1 test in elite female rugby league players.
This study aims to establish the validity and reliability of the prone Yo-YoIRL1 in elite female rugby league players (part one) and determine the anthropometric and physical characteristics contributing to 15m prone Yo-YoIRL1 performance (part two). Part one, 21 subjects completed one Yo-YoIRL1, one 20m and two 15m prone Yo-YoIRL1 tests over four sessions, with 7-14 days in-between. Part two, ten subjects completed a testing battery, including body mass, height, dual-energy x-ray absorptiometry, isometric mid-thigh pull, isometric bench-press, 10m and 20m sprints and an incremental treadmill test ([Formula: see text]). The 15m prone YoYoIRL1 demonstrated poor reliability with a typical error of 68m (21%) and a smallest worthwhile change of 54m (9%). Validity analysis found the prone versions of the YoYoIRL1 were not sensitive measures of intermittent running performance. Both prone YoYoIRL1 test distances demonstrated large mean bias (76% and -37% respectively) and typical error of the estimate (19% and 21%, respectively) in comparison to the YoYoIRL1. Body mass (r = -0.89), lean mass (r = -0.64), body fat % (r = -0.68), [Formula: see text] (l∙min-1) (r = -0.64), IMTP (r = -0.69), IBP (r = -0.15), 10m (r = -0.77) and 20m (r = -0.72) momentum displayed large negative relationships with 15m prone Yo-YoIRL1 performance. Due to the poor validity of the 20m prone YoYoIRL1, the poor validity and reliability of the 15m prone YoYoIRL1, and the anthropometric and physical characteristics which negatively impact performance, practitioners should reconsider the use of the prone YoYoIRL1 test to monitor high intensity intermittent running performance.
Topics: Humans; Female; Exercise Test; Reproducibility of Results; Young Adult; Adult; Football; Athletic Performance; Running; Athletes; Absorptiometry, Photon; Rugby
PubMed: 38924067
DOI: 10.1371/journal.pone.0306171